It should not be used or only used with caution in people withheart failure and people with asthma. It may mask signs of low blood sugar in people with diabetes and it may mask signs of hyperthyroidism.[1]
Animal studies showed some signs of potential trouble for women who are pregnant, and it has not been tested in women who are pregnant. It is not known if penbutolol is secreted in breast milk.[1]
Penbutolol is able to bind to both beta-1 adrenergic receptors andbeta-2 adrenergic receptors (the two subtypes), thus making it a non-selective β blocker.[2]: Table 10–2, p 252 Penbutolol is asympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors.[3]
Penbutolol acts on the β1 adrenergic receptors in both the heart and the kidney. When β1 receptors are activated by acatecholamine, they stimulate a coupledG protein which activates adenylyl to convertadenosine triphosphate (ATP) tocyclic adenosine monophosphate (cAMP). The increase in cAMP ultimately alters the movement of calcium ions in heart muscle and increases heart rate.[2]: 213–214 Penbutolol blocks this and decreases heart rate, which lowers blood pressure.[10]: 40
The ability of penbutolol to act as apartial agonist proves useful in the prevention ofbradycardia as a result of decreasing the heart rate excessively.[3] Penbutolol binding β1 adrenergic receptors also alters kidney functions. Under normal physiological conditions, the enzyme renin convertsangiotensinogen toangiotensin I, which will then be converted toangiotensin II. Angiotensin II stimulates the release ofaldosterone from theadrenal gland, causing a decrease inelectrolyte and water retention, ultimately increasing water excretion and decreasing blood volume and pressure.[11]: 221
Penbutolol is rapidly absorbed from the gastrointestinal tract, has abioavailability over 90%,[8] and has a rapid onset of effect. Penbutolol has ahalf life of five hours.[2]: Table 10–2, p 252
The experimentallog P of penbutolol is 4.15.[14][15] Penbutolol showed the second highest predicted lipophilicity of 30clinically relevant beta blockers, with the most lipophilic beta blocker predicted to be the lesser-knownbopindolol.[16]
Penbutolol was approved by the FDA in 1987.[4] In January 2015 the FDA acknowledged that the penbutolol was no longer marketed in the US, and determined that the drug was not withdrawn for safety reasons.[5]
^Schoenberger JA (Jun 1989). "Usefulness of penbutolol for systemic hypertension. Penbutolol Research Group".Am J Cardiol.63 (18):1339–42.doi:10.1016/0002-9149(89)91045-x.PMID2658525.
^Berdeaux A, Duhaze P, Giudicelli JF (1982). "Pharmacological analysis of beta adrenoceptor blockade-induced coronary blood flow redistribution in dogs using l-penbutolol".The Journal of Pharmacology and Experimental Therapeutics.221 (3):740–747.PMID6123586.
^Dent, M. R., Singal, T., Tappia, P. S., Sethi, R., Dhall, N. S. (2008). β-Adrenoceptor-Linked Signal Transduction Mechanisms in Congestive Heart Failure. Chapter 2, pp 27-49 in Signal transduction in the cardiovascular system in health and disease, Eds Srivastava, Ashok K., Anand-Srivastava, Madhu B. Springer Science & Business Media, 2008ISBN9780387095523
^Finkel, Richard; Clark, Michelle A.; Cubeddu, Luigi X. Lippincott's Illustrated Reviews: Pharmacology, 4th Edition Lippincott Williams & Wilkins, 2009.ISBN9780781771559
^Langlois M, Brémont B, Rousselle D, Gaudy F (1993). "Structural analysis by the comparative molecular field analysis method of the affinity of beta-adrenoreceptor blocking agents for 5-HT1A and 5-HT1B receptors".Eur. J. Pharmacol.244 (1):77–87.doi:10.1016/0922-4106(93)90061-d.PMID8093601.
^Glennon RA. Strategies for the Development of Selective Serotonergic Agents. Chapter 4 in The Serotonin Receptors: From Molecular Pharmacology to Human Therapeutics. Ed. Bryan L. Roth. Springer Science & Business Media, 2008ISBN9781597450805
^Mannhold R (February 2005). "The impact of lipophilicity in drug research: a case report on beta-blockers".Mini Rev Med Chem.5 (2):197–205.doi:10.2174/1389557053402701.PMID15720289.
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